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Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances
Author(s) -
McMurray John J.V.
Publication year - 2015
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.250
Subject(s) - neprilysin , sacubitril , heart failure , medicine , valsartan , enalapril , bradykinin , cardiology , angiotensin converting enzyme , pharmacology , ejection fraction , receptor , blood pressure , enzyme , chemistry , biochemistry
This review describes the role of neprilysin (also known as neutral endopeptidase or enkephalinase) in the degradation of natriuretic and other vasoactive peptides, including bradykinin and adrenomedullin. The initial development of neprilysin inhibitors, then angiotensin converting enzyme‐neprilysin inhibitors and, most recently, the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 (sacubitril valsartan) as an extension of the nurohumoral basis for the treatment of heart failure is also summarised. Finally, the implications of the compelling benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF) is discussed.